1. Field of the Invention
The present invention relates to a novel extracted substance useful for inhibition of the human immunodeficiency virus (HIV) and a process for extracting the same. Specifically, the extract is prepared from a mixture of a non-fat starch from Ricini semen and a root of Coptis which exhibits a suitable anti-HIV activity.
2. Description of the Prior Art
All references of the scientific and patent literature cited herein are hereby incorporated in their entirety by reference by such citation.
In 1983, it was found that HIV-1 is the causative agent of acquired immunodeficiency syndrome (AIDS). Thereafter, the genome of the virus was cloned and several approaches to discover inhibitors of HIV have been followed.
The selective infection of helper T cells (TH) by HIV induces a disorder of the immune system and subsequently results in AIDS. The reverse transcribed viral genome usually remains in the chromosome of host cells in the latent period. At the end of the latent period, viral proliferation induces cell fusions that produce syncytia, and subsequently kill cells by an acute infection. In the absence of syncytium formation, the viral proliferation continues in a chronic infection, without any significant cytopathic effects.
The membrane protein gp 120 of the virus recognizes CD4 receptors present in host cells; the virus binds to the CD4 receptor through this recognition event. The virus enters cells and subsequently copies its RNA genome into a DNA copy using a reverse transcriptase. The reverse transcribed viral genome then integrates into the chromosomal DNA of host cells.
The viral genome is replicated in the cells by several signals and factors required for host cell proliferation. Viral proteins are then produced, a process which requires the action of trans-acting regulatory proteins encoded by the viral genome. Post-translational processing of the viral proteins for assembly of complete virus particles involves the action of an HIV-specific protease and also glycosylation of some viral proteins.
Accordingly, in order to develop anti-HIV drugs, inhibitors of the following functions of the viral replication cycle should be developed as chemotherapies.
(a) inhibition of interactions between gp120 of the virus and CD4 receptors of host cells, PA1 (b) inhibition of the action of reverse transcriptase in changing RNA of the virus into proviral DNA, PA1 (c) inhibition of activities of viral regulatory proteins, PA1 (d) inhibition of cleavage of viral precursor proteins, PA1 (e) inhibition of an action of a glucosidase or a mannosidase for a prevention of glycosylation of viral proteins and so forth.
A number of drugs having selective anti-viral efficacy have hitherto been developed using differences between HIV and human host cells. Such drugs, especially drugs inhibiting viral proliferation, include dextran sulfates and peptide T having an inhibitory function of (a) described above; dideoxycytidines, dideoxyinosines and phosphonoformates having a function of (b). Beside these are the examples of ribavirin, castanospermine, GLQ 223, antisense oligonucleotides, protease inhibitors, and so forth. However, these drugs are still not commercially available for AIDS.
In addition, zidovudine (azidothymidine, AZT) is currently used as a medicine for AIDS, but has serious disadvantages in that it usually induces side effects including symptoms such as headaches, emesis, high fevers, injury of the hematopoietic system and nervous system, and suppression of the liver function. Also resistance to AZT is often found in long-term therapy.
We, the inventors of the present invention, have intensively conducted a wide range of experiments in order to develop potent HIV inhibitors having good therapeutic effects. As a result, we have discovered that a novel extracted substance isolated from Ricini semen and a root of Coptis has significantly improved anti-HIV activity, and could provide a good therapy for HIV infection.